ULTRALONG COMPLEMENTARITY DETERMINING REGIONS AND USES THEREOF

• US 20140050720A1
• Filed: 01/09/2013
• Published: 02/20/2014
• Est. Priority Date: 01/09/2012
• Status: Abandoned Application

• Current Assignee: The Scripps Research Institute
• Original Assignee: The Scripps Research Institute
• Inventors: Smider, Vaughn, Bazirgan, Omar A., Ekiert, Dan, Mao, Hongyuan Helen, Schultz, Peter, Wang, Feng, Wilson, Ian, Zhang, Yong
• Application Number:
  US13/737,913
• Publication Number:
  US 20140050720A1
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/53 Colony-stimulating factor [CSF]
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/10 from RNA viruses
• CPC Class Codes: C07K 16/46 Hybrid immunoglobulins hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00
• CPC Class Codes: C07K 2317/20 characterized by taxonomic origin
• CPC Class Codes: C07K 2317/50 characterized by immunoglobulin fragments
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/569 Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: C07K 2318/00 Antibody mimetics or scaffolds
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/50 containing protease site
• CPC Class Codes: C07K 2319/55 containing a fusion with a toxin, e.g. diphteria toxin
• CPC Class Codes: C12N 15/09 Recombinant DNA-technology
• CPC Class Codes: C12N 15/62 DNA sequences coding for fusion proteins
• CPC Class Codes: C12N 15/63 : Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• CPC Class Codes: C12N 5/00 : Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor; plant reproduction by tissue culture techniques A01H4/00

Abstract

Disclosed herein are immunoglobulin constructs comprising at least one immunoglobulin domain or fragment thereof; and a therapeutic polypeptide or derivative or variant thereof attached to or inserted into said immunoglobulin domain. Also provided are immunoglobulin constructs comprising a mammalian immunoglobulin heavy chain comprising at least a portion of a knob domain in the complementarity-determining region 3 (CDR3H) or fragment thereof; and a therapeutic polypeptide attached to or inserted into said knob domain of the CDR3H. Also provided are immunoglobulin constructs comprising a mammalian immunoglobulin heavy chain comprising at least a portion of a stalk domain in the complementarity-determining region 3 (CDR3H) or fragment thereof; and a therapeutic polypeptide attached to or inserted into said stalk domain of the CDR3H. Also described herein are methods and compositions comprising the immunoglobulin constructs described herein for treatment and prevention of a disease or condition in a subject.

Claims

1. A library of antibodies or binding fragments thereof, wherein the antibodies or binding fragments thereof comprise an ultralong CDR3.

2. A library of polynucleotides encoding for antibodies or binding fragments thereof, wherein the encoded antibodies or binding fragments thereof comprise an ultralong CDR3.

3-47. -47. (canceled)

48. A recombinant antibody or fragment thereof, wherein at least a portion of the recombinant antibody or fragment thereof is based on or derived from at least a portion of an ultralong CDR3.

160. A library of antibodies or binding fragments thereof, wherein the antibodies or binding fragments thereof comprise the antibody or binding fragment of claim 48.

162. A nucleic acid library comprising a plurality of polynucleotides comprising sequences coding for antibodies or binding fragments thereof, wherein the antibodies or binding fragments thereof comprise the antibody or binding fragment of claim 48.

166. A polynucleotide comprising a nucleic acid sequence that encodes the antibody or binding fragment thereof of claim 48.

167. A vector comprising a polynucleotide, wherein the polynucleotide comprises a nucleic acid sequence that encodes the antibody or binding fragment thereof of claim 48.

168. A host cell comprising a polynucleotide, wherein the polynucleotide comprises a nucleic acid sequence that encodes the antibody or binding fragment thereof of claim 48.

169. A method of producing an antibody or binding fragment thereof comprising an ultralong CDR3 or fragment thereof comprising culturing the host cell of claim 168 under conditions wherein the polynucleotide sequence is expressed and the antibody or binding fragment thereof comprising an ultralong CDR3 or fragment thereof is produced.

171. A pharmaceutical composition comprising an antibody or fragment thereof of claim 48.

175. A method of treating a disease or condition in a subject in need thereof comprising administering to the mammal a therapeutically effective amount of the antibody of claim 48.

49. An antibody or fragment thereof comprising:

(a) a first antibody sequence, wherein at least a portion of the first antibody sequence is derived from at least a portion of an ultralong CDR3;

(b) a non-antibody sequence; and

(c) optionally, a second antibody sequence, wherein at least a portion of the second antibody sequence is derived from at least a portion of an ultralong CDR3.

189. A library of antibodies or binding fragments thereof, wherein the antibodies or binding fragments thereof comprise the antibody or binding fragment of claim 49.

190. A nucleic acid library comprising a plurality of polynucleotides comprising sequences coding for antibodies or binding fragments thereof, wherein the antibodies or binding fragments thereof comprise the antibody or binding fragment of claim 49.

191. A polynucleotide comprising a nucleic acid sequence that encodes the antibody or binding fragment thereof of claim 49.

192. A vector comprising a polynucleotide, wherein the polynucleotide comprises a nucleic acid sequence that encodes the antibody or binding fragment thereof of claim 49.

193. A host cell comprising a polynucleotide, wherein the polynucleotide comprises a nucleic acid sequence that encodes the antibody or binding fragment thereof claim 49.

194. A method of producing an antibody or binding fragment thereof comprising an ultralong CDR3 or fragment thereof comprising culturing the host cell of claim 193 under conditions wherein the polynucleotide sequence is expressed and the antibody or binding fragment thereof comprising an ultralong CDR3 or fragment thereof is produced.

50-158. -158. (canceled)

159. A library of antibodies or binding fragments thereof, wherein the antibodies or binding fragments thereof comprise an ultralong CDR3.

161. A nucleic acid library comprising a plurality of polynucleotides comprising sequences coding for antibodies or binding fragments thereof, wherein the antibodies or binding fragments thereof comprise an ultralong CDR3.

163-165. -165. (canceled)

170. (canceled)

172. A pharmaceutical composition comprising (a) an antibody or fragment thereof comprising sequence based on or derived from at least a portion of an ultralong CDR3;

and (b) a pharmaceutically acceptable excipient.

173-174. -174. (canceled)

176-188. -188. (canceled)